Interferon gamma inducible protein 10 (IP-10) (also known as CXCL10) is a 10 kDa chemokine that is secreted by a variety of cells, including endothelial cells, monocytes, fibroblasts, and keratinocytes, in response to IFN-gamma. IP-10 is also present in dermal macrophages and endothelial cells in delayed type hypersensitivity (DTH) responses in human. Although originally identified based on its being induced by IFN-gamma, IP-10 can also be induced by IFN-alpha, for example in dendritic cells. IP-10 expression can also be induced in cells of the central nervous system, such as astrocytes and microglia, by stimuli such as IFN-gamma, viruses and lipopolysaccharide.
The receptor for IP-10 has been identified as CXCR3, a seven transmembrane receptor. CXCR3 is expressed on activated T lymphocytes but not on resting T lymphocytes, nor on B lymphocytes, monocytes or granulocytes. CXCR3 expression is upregulated on NK cells by stimulation with TGF-beta 1. Two other ligands for CXCR3 are identified: MIG and ITAC. Binding of IP-10 to CXCR3 mediates calcium mobilization and chemotaxis in activated T cells. Chemotaxis and intracellular calcium mobilization are also induced by IP-10 binding to CXCR3 on activated NK cells. Within the thymus, IP-10 is a chemoattractant for TCRαβ+ CD8+ T cells, TCRγδ+ T cells and NK-type cells.
IP-10 or its receptor CXCR3 have been identified in a variety of different inflammatory and autoimmune conditions, including multiple sclerosis, rheumatoid arthritis, ulcerative colitis, hepatitis, spinal cord injury, systemic lupus erythematosus, transplant rejection, Sjögren's syndrome. Accordingly, there is a need for therapeutic agents (e.g., anti-IP-10 antibodies) as well as methods for the treatment of IP-10 related diseases (e.g., inflammatory and autoimmune conditions).